EP2898821B1 - Transdermales Mikronadel-Array-Pflaster und Herstellungsverfahren dafür - Google Patents

Transdermales Mikronadel-Array-Pflaster und Herstellungsverfahren dafür Download PDF

Info

Publication number
EP2898821B1
EP2898821B1 EP14171688.6A EP14171688A EP2898821B1 EP 2898821 B1 EP2898821 B1 EP 2898821B1 EP 14171688 A EP14171688 A EP 14171688A EP 2898821 B1 EP2898821 B1 EP 2898821B1
Authority
EP
European Patent Office
Prior art keywords
hole
sheet
barbule
microneedle
barbules
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
EP14171688.6A
Other languages
English (en)
French (fr)
Other versions
EP2898821A1 (de
Inventor
Juang-Tang Huang
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Micro Nipple Technology Co Ltd
Original Assignee
Micro Nipple Technology Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Micro Nipple Technology Co Ltd filed Critical Micro Nipple Technology Co Ltd
Publication of EP2898821A1 publication Critical patent/EP2898821A1/de
Application granted granted Critical
Publication of EP2898821B1 publication Critical patent/EP2898821B1/de
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
    • A61B5/685—Microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14546—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
    • A61B5/1473—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means invasive, e.g. introduced into the body by a catheter
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/150007—Details
    • A61B5/150015—Source of blood
    • A61B5/150022—Source of blood for capillary blood or interstitial fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/150007—Details
    • A61B5/150206—Construction or design features not otherwise provided for; manufacturing or production; packages; sterilisation of piercing element, piercing device or sampling device
    • A61B5/150274—Manufacture or production processes or steps for blood sampling devices
    • A61B5/150282—Manufacture or production processes or steps for blood sampling devices for piercing elements, e.g. blade, lancet, canula, needle
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/150969—Low-profile devices which resemble patches or plasters, e.g. also allowing collection of blood samples for testing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B37/00—Methods or apparatus for laminating, e.g. by curing or by ultrasonic bonding
    • B32B37/14—Methods or apparatus for laminating, e.g. by curing or by ultrasonic bonding characterised by the properties of the layers
    • B32B37/24—Methods or apparatus for laminating, e.g. by curing or by ultrasonic bonding characterised by the properties of the layers with at least one layer not being coherent before laminating, e.g. made up from granular material sprinkled onto a substrate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/04—Arrangements of multiple sensors of the same type
    • A61B2562/046—Arrangements of multiple sensors of the same type in a matrix array
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/12—Manufacturing methods specially adapted for producing sensors for in-vivo measurements
    • A61B2562/125—Manufacturing methods specially adapted for producing sensors for in-vivo measurements characterised by the manufacture of electrodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14507—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue specially adapted for measuring characteristics of body fluids other than blood
    • A61B5/1451—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue specially adapted for measuring characteristics of body fluids other than blood for interstitial fluid
    • A61B5/14514—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue specially adapted for measuring characteristics of body fluids other than blood for interstitial fluid using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/150977—Arrays of piercing elements for simultaneous piercing
    • A61B5/150984—Microneedles or microblades
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/683—Means for maintaining contact with the body
    • A61B5/6832—Means for maintaining contact with the body using adhesives
    • A61B5/6833—Adhesive patches
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B37/00—Methods or apparatus for laminating, e.g. by curing or by ultrasonic bonding
    • B32B37/14—Methods or apparatus for laminating, e.g. by curing or by ultrasonic bonding characterised by the properties of the layers
    • B32B37/24—Methods or apparatus for laminating, e.g. by curing or by ultrasonic bonding characterised by the properties of the layers with at least one layer not being coherent before laminating, e.g. made up from granular material sprinkled onto a substrate
    • B32B2037/243—Coating
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B2535/00—Medical equipment, e.g. bandage, prostheses, catheter
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T156/00—Adhesive bonding and miscellaneous chemical manufacture
    • Y10T156/10—Methods of surface bonding and/or assembly therefor

Definitions

  • the invention relates to a transdermal microneedle array patch, particularly a transdermal microneedle array patch which obtains physiologic data of a human body by measuring the concentration of hypodermal target molecules.
  • Tissue fluid is mainly contained in subcutaneous tissue and includes amino acids, sugars, fatty acids, coenzymes, hormones, neurotransmitters, salts and waste products from the cells. Moreover, the tissue fluid is also the major communication channel for cell and blood. The concentrations of the various components in the tissue fluid are useful for determining user's physiological conditions.
  • the medicine will be slowly released over a long period in tissue fluid when the patient takes or injects the medicine.
  • the concentration variation of medicine in the tissue fluid is continually monitored during development of medicine and clinical experiment. Therefore, the tissue fluid is commonly sampled to further examine or analyze in medical treatment of patient.
  • the commercially available physiological examination instruments generally withdraw tissue fluid by using a needle piercing through stratum corneum.
  • the patient may feel painful for this kind of invasive sampling way.
  • the patient may be infected by microorganism originally present on epidermis and entering the patient body as the stratum corneum is pierced by a needle.
  • Transdermal sensor with array-arranged microneedles pricking through skin is developed to withdraw tissue fluid in painless and minimally-invasive way.
  • the array-arranged microneedles of a transdermal sensor can be manufactured with standard semiconductor process such as photolithograph process and etching process.
  • US Pat. No. 7,344,499 discloses a process for manufacturing silicon microneedles.
  • a silicon wafer with a first patterned photoresist layer is prepared.
  • a through hole is defined on the wafer by anisotropic etching.
  • a chromium layer is coated on the wafer and a second patterned photoresist layer is formed atop the through hole to function as circular etching mask.
  • the wafer is then etched to form outer tapered wall for the microneedles.
  • the silicon-based microneedles are brittle and tend to break when the microneedles prick through user's skin.
  • hollow microneedles with resin barbules are proposed, where the barbules are drilled by laser processing.
  • sheet with barbules is formed by extruding polyimide or polyether ether ketone, and then the barbules are drilled by laser to form hollow microneedles.
  • the microneedles have compact size such that the barbules may have ragged edge after extrusion.
  • WO 2005 049 108 A relates to a system and method for transdermally delivering a biologically active agent comprising one or more electrodes having stratum corneum-piercing projections and a circuit that delivers an electrical signal to the electrodes to electroporate a cell membrane.
  • the system is configured to generate homogeneous electrical fields and, more preferably, to generate spherically or semispherically symmetrical electric fields.
  • Methods of the invention include applying a first electric signal to facilitate transdermal transport of the agent and applying a second electric signal to facilitate intracellular transport of the agent.
  • US 2013 225 956 A relates to a transdermal sensor for detecting a concentration of a hypodermal target molecule, comprising: a substrate; a plurality of microneedles fixed on said substrate; a signal processing unit, which is electrically connected to said microneedles; and a power supply unit for providing the working power.
  • the transdermal sensor detects a long-term, real-time concentration of a hypodermal target molecule for a doctor to evaluate a physiological status of a user with minimal invasive piercing and pain.
  • One object of the present invention is to provide a transdermal microneedle array patch, where the transdermal microneedle array patch has microneedles made by punching or etching to have sufficient mechanical strength.
  • the microneedle can be kept intact after the microneedle pricks user's skin for sensing.
  • the microneedle has such structure that the sensing polymer can be advantageously coated on inner surface of the tip of the microneedle. The sensing polymer can be prevented from falling as the microneedle pricks user's skin for sensing.
  • the present invention provides a transdermal microneedle array patch.
  • the transdermal microneedle array patch includes a substrate, a microneedle unit, a signal processing unit and a power supply unit.
  • the microneedle unit at least comprises a first microneedle set used as a working electrode and a second microneedle set used as a reference electrode, the first and second microneedle sets arranging on the substrate.
  • Each microneedle set comprises at least a microneedle.
  • the first microneedle set comprises at least a sheet having a through hole on which a barbule forms at the peripheral. One of the sheets provides the through hole from which the barbules at the edge of the other sheets go through, and the barbules are disposed separately.
  • the microneedles of the working electrode of the transdermal microneedle array patch according to the invention may be subjected to surface modification, in view of the target molecule to be sensed.
  • the target molecule may be a biological molecule, such as glucose, cortisol or fatty acids.
  • the target molecule may be a pharmaceutical molecule, such as antibiotics.
  • the transdermal microneedle array patch of the present invention may be used for pharmaceutical monitoring during the administration of a medication for a chronic disease or a specific pharmaceutical. Personalized medication of a specific dosage or frequency of administration can be provided based on the individual metabolism of the pharmaceutical.
  • the microneedle of the present invention has sufficient mechanical strength.
  • the microneedle can be kept intact after the microneedle pricks user skin for sensing.
  • the microneedle has simple manufacture process, which is beneficial for mass production.
  • Fig. 1 shows the exploded view of the transdermal microneedle array patch according to a first embodiment of the present invention from one viewing direction
  • Fig. 2 shows the exploded view of the transdermal microneedle array patch from another viewing direction.
  • the transdermal microneedle array patch of the present invention mainly comprises a substrate 10, a microneedle unit 20 (comprising a plurality of sheets; that are not explicitly shown), a flexible pad 30, a signal processing unit 41, a power supply unit 43 and a cover 50, where the signal processing unit 41 and the power supply unit 43 are arranged on a circuit board 40.
  • the microneedle unit 20 comprises a first microneedle set 22 used as a working electrode, a second microneedle set 24 used as a reference electrode, and a third microneedle set 26 used as a counter electrode.
  • the flexible pad 30 has an opening 32 through which the microneedle unit 20 passes.
  • the microneedle unit 20 further comprises electric conducting posts 21, 23, 25 to respectively and electrically connect to the contacts 42, 44 and 46 on the circuit board 40.
  • the transdermal microneedle array patch of the present invention uses the flexible pad 30 to have tight fit with the user's muscle during operating thereof.
  • the signal processing unit 41 electrically connects to the microneedle unit 20 and receives a concentration data of hypodermal target molecules sensed by the microneedle unit 20.
  • the signal processing unit 41 generates a sensing signal manifesting the current physiological condition of user after processing the received concentration data.
  • the power supply unit 43 provides working power to the transdermal microneedle array patch of the present invention.
  • Fig. 3 shows a schematic exploded view of the microneedle unit 20 of the first embodiment of the present invention.
  • the first microneedle set 22 comprises a plurality of sheets, namely a first sheet 222 and a second sheet 224 stacked with the first sheet 222.
  • the first sheet 222 has at least one first through hole 2222 defined thereon, and a first barbule 2224 at peripheral of the first through hole 2222.
  • the second sheet 224 has at least one second through hole 2242 defined thereon, and a second barbule 2244 at peripheral of the second through hole 2242, where the second barbule 2244 penetrates the first through hole 2222 to juxtapose the first barbule 2224.
  • the through hole (2222) on one sheet (namely the first sheet) is penetrated by the barbules of the other sheet (2244) or sheets.
  • the second sheet 224 of the first microneedle set 22 comprises barb 2246 at the peripheral thereof and matched with the aperture 102 defined on the substrate 10.
  • the second sheet 224 of the first microneedle set 22 comprises conductive pin 2248 at the peripheral thereof.
  • the conductive pin 2248 can be inserted into a slot 104 defined on the substrate 10 to electrically connect to the conductive post 21.
  • the second microneedle set 24 comprises a first sheet 242.
  • the first sheet 242 has at least one first through hole 2422 defined thereon, and a first barbule 2424 at peripheral of the first through hole 2422.
  • the first sheet 242 of the second microneedle set 24 comprises barb 2426 at the peripheral thereof and matched with the aperture 102 defined on the substrate 10.
  • the first sheet 242 of the second microneedle set 24 comprises conductive pin 2428 at the peripheral thereof.
  • the conductive pin 2428 can be inserted into a slot 104 defined on the substrate 10 to electrically connect to the conductive post 23.
  • the third microneedle set 26 also comprises a first sheet 262.
  • the first sheet 262 has at least one first through hole 2622 defined thereon, and a first barbule 2624 at peripheral of the first through hole 2622.
  • the first sheet 262 of the third microneedle set 26 comprises barb 2626 at the peripheral thereof and matched with the aperture 102 defined on the substrate 10.
  • the first sheet 262 of the third microneedle set 26 comprises conductive pin 2628 at the peripheral thereof. The conductive pin 2628 can be inserted into a slot 104 defined on the substrate 10 to electrically connect to the conductive post 25.
  • the first microneedle set 22, the second microneedle set 24, and the third microneedle set 26 can be made by punching or etching process.
  • the material of the barbules is selected from the group consisting of stainless steel, nickel, nickel alloy, titanium, titanium alloy, carbon nanotube, and silicon.
  • the surface of the barbules is coated with biologically compatible metal.
  • the material of the barbules can also be selected from the group consisting of polycarbonate, polymethacrylic acid, polytetrafluoroethylene, and polyester.
  • the surface of the barbules is also coated with biologically compatible metal.
  • the height of the barbules is 300-600 micrometers; the base width of the barbules is 150-450 micrometers.
  • the separation between tips of the barbules is 500-3000 micrometers.
  • Fig. 4 is a top view of the microneedle set functioning as working electrode of the first embodiment of the present invention.
  • the first microneedle set 22 comprises a first sheet 222 and a second sheet 224 stacked with the first sheet 222.
  • the first sheet 222 has at least one first through hole 2222 defined thereon, and a first barbule 2224 at peripheral of the first through hole 2222.
  • the second sheet 224 has at least one second through hole 2242 defined thereon, and a second barbule 2244 at peripheral of the second through hole 2242, where the second barbule 2244 penetrates the first through hole 2222 to juxtapose the first barbule 2224.
  • Fig. 5 is a top view of the microneedle set functioning as working electrode according to a second embodiment of the present invention.
  • the first microneedle set 22 comprises a first sheet 222, a second sheet 224 and a third sheet 226 stacked with each other.
  • the first sheet 222 has at least one first through hole 2222 defined thereon, and a first barbule 2224 at peripheral of the first through hole 2222.
  • the second sheet 224 has at least one second through hole 2242 defined thereon, and a second barbule 2244 at peripheral of the second through hole 2242.
  • the third sheet 226 has at least one third through hole 2262 defined thereon, and a third barbule 2264 at peripheral of the third through hole 2262.
  • the second barbule 2244 and the third barbule 2264 penetrates the first through hole 2222 to juxtapose the first barbule 2224, and the tips of the barbules are in right triangular arrangement from top view.
  • Fig. 6 is a top view of the microneedle set functioning as working electrode according to a third embodiment of the present invention.
  • the first microneedle set 22 comprises a first sheet 222, a second sheet 224 and a third sheet 226 stacked with each other.
  • the first sheet 222 has at least one first through hole 2222 defined thereon, and a first barbule 2224 at peripheral of the first through hole 2222.
  • the second sheet 224 has at least one second through hole 2242 defined thereon, and a second barbule 2244 at peripheral of the second through hole 2242.
  • the third sheet 226 has at least one third through hole 2262 defined thereon, and a third barbule 2264 at peripheral of the third through hole 2262.
  • the second barbule 2244 and the third barbule 2264 penetrates the first through hole 2222 to juxtapose the first barbule 2224, and the tips of the barbules are in isosceles triangular arrangement from top view.
  • Fig. 7 is a top view of the microneedle set functioning as working electrode according to a fourth embodiment of the present invention.
  • the first microneedle set 22 comprises a first sheet 222, a second sheet 224, a third sheet 226 and a fourth sheet 228 stacked with each other.
  • the first sheet 222 has at least one first through hole 2222 defined thereon, and a first barbule 2224 at peripheral of the first through hole 2222.
  • the second sheet 224 has at least one second through hole 2242 defined thereon, and a second barbule 2244 at peripheral of the second through hole 2242.
  • the third sheet 226 has at least one third through hole 2262 defined thereon, and a third barbule 2264 at peripheral of the third through hole 2262.
  • the fourth sheet 228 has at least one fourth through hole 2282 defined thereon, and a fourth barbule 2284 at peripheral of the fourth through hole 2282.
  • the second barbule 2244, the third barbule 2264 and the fourth barbule 228 penetrates the first through hole 2222 to juxtapose the first barbule 2224, and the tips of the barbules are in rectangular arrangement from top view.
  • the barbule 2224 of the first microneedle set 22 comprises a tip 2221 and a base 2223.
  • the tips of those barbules, after the sheets are stacked together, are not at the same altitudes. Namely, some barbules pass more through holes than other barbules.
  • the height of the barbules can be such designed, based on the stacked order of sheets, that the tips of those barbules, after the sheets are stacked together, are at the same altitudes.
  • Fig. 8 shows a perspective of an assembled transdermal microneedle array patch according to the first embodiment of the present invention, wherein the first microneedle set 22 comprises a plurality of sheets (not explicitly shown).
  • Fig. 9 shows a sectional of an assembled transdermal microneedle array patch based on the first embodiment of the present invention.
  • the first microneedle set 22 comprises a first sheet 222 and a second sheet 224 stacked with each other.
  • the first sheet 222 and the second sheet 224 can be assembled by punching peripherals thereof.
  • the second microneedle set 24 comprises only a first sheet 242 and the third microneedle set 26 comprises only a first sheet 262.
  • the transdermal microneedle array patch of the present invention uses the flexible pad 30 to have tight fit with the user's muscle during operation thereof.
  • the first microneedle set 22 of the present invention of the working electrode of the transdermal microneedle array patch according to the invention may be subjected to surface modification, in view of the target molecule to be sensed.
  • the target molecule may be a biological molecule, such as glucose, cortisol or fatty acids.
  • the target molecule may be a pharmaceutical molecule, such as antibiotics.
  • the transdermal microneedle array patch of the present invention may be used for pharmaceutical monitoring during the administration of a medication for a chronic disease or a specific pharmaceutical. Personalized medication of a specific dosage or frequency of administration can be provided based on the individual metabolism of the pharmaceutical.
  • the first microneedle set 22 may be subjected to surface modification, in view of the target molecule to be sensed. Specifically, a molecule selected from the group consisting of an antibody, an aptamer, a single-chain variable fragment (ScFv), a carbohydrate, and a combination thereof, may be coated on the surface of the microneedles.
  • the first microneedle set 22 of the working electrode is modified with glucose oxidase (GOx) for sensing (blood) glucose.
  • GOx glucose oxidase
  • SAM self-assembled monolayer
  • a blocking molecule is applied to the position that the antibody or the aptamer fails to be coupled on SAM.
  • carbon nanotubes may be further mixed into the gold layer. Below the various methods for manufacturing modified electrodes are described.
  • the method for manufacturing streptavidin-modified electrode includes steps as below.
  • the working electrode deposited with a gold layer was treated with 200 mM of 3,3-dithiodipropionic acid for 30 min to form a self-assembled monolayer (SAM), and then washed thoroughly with distilled water.
  • SAM self-assembled monolayer
  • the activation of carboxylic groups were performed on the electrode after incubation with 100 mM of N-(3-dimethylaminopropyl)-N-ethylcarbodiimide (EDC) and 1 mM N-hydroxysuccinimide (NHS) for an hour. Afterwards, the electrode was incubated overnight with 1 mg/ml streptavidin in PBS buffer (pH 7.5).
  • Tetracycline is an antibiotic commonly used for treating organ inflammation of a patient.
  • a transdermal microneedle array patch coupling a biotinylated ssDNA aptamer on a surface of the microneedle of streptavidin-modified electrode is suitable to measure the concentration of tetracycline, wherein the biotinylated ssDNA aptamer has specificity to tetracycline. Therefore, the transdermal microneedle array patch of the present invention may be used for pharmaceutical monitoring during the administration of a medication for a chronic disease or a specific pharmaceutical. Personalized medication of a specific dosage or frequency of administration can be provided based on the individual metabolism of the pharmaceutical.
  • MWCNT multiwalled carbon nanotube
  • the method for manufacturing multiwalled carbon nanotube (MWCNT) chemically modified electrode includes steps as below.
  • Carboxylic derivative of CNTs was obtained from commercial available MWCNTs by refluxing in 4 M HNO 3 .
  • the thus obtained oxidized MWCNTs (20 mg) were refluxed in SOCl 2 (10 mL) for 12 h.
  • the resulting mixture was decanted, and excess SOCl 2 was removed in vacuo.
  • a solution of mercaptoethanol (2 mL, 30 mmol) and of triethylamine (1 mL, 7 mmol) in CH 2 Cl 2 (10 mL) was added, and the mixture was refluxed for 24 h.
  • the suspension was centrifuged and the solid repeatedly washed with methanol to give derivatized MWCNTs.
  • the MWCNTs-CME was prepared by dipping the cleaned gold electrode in a sonicated suspension of 3 mg of derivatized nanotubes in 1 mL of DMSO for 48 h. Finally, 10 nM of biotinylated DNA aptamer was incubated on streptavidin coated electrode for 40 min, and washed thoroughly with distilled water.
  • the method for manufacturing single-walled carbon nanotube (SWCNT) chemically modified electrode includes steps as below.
  • Carboxylic derivative of CNTs was obtained from commercial available SWCNTs by refluxing in 4 M HNO 3 .
  • a cystamine monolayer was assembled on the gold electrode to form a self-assembled monolayer (SAM) and the SWCNTs (reactant 2a) that was dispersed by sonicating 3 mg of the material in 1 mL of DMF were linked to the SAM surface in the presence of the coupling reagent, 1,3-dicyclohexylcarbodiimide (DCC, 3 mg) to obtain a product 2b.
  • SAM self-assembled monolayer
  • DCC 1,3-dicyclohexylcarbodiimide
  • mercaptoethanol was coupled to the carboxyl groups at the free edges of the product 2b by using DCC (2 mM mercaptoethanol solution in 1 mL of DMF and 3 mg of DCC) to obtain SWCNT chemically modified electrode.
  • DCC 2 mM mercaptoethanol solution in 1 mL of DMF and 3 mg of DCC
  • 10 nM of biotinylated DNA aptamer was incubated on streptavidin coated electrode for 40 min, and washed thoroughly with distilled water.
  • Fig. 10 refers to a further development of the first embodiment and shows a partially sectional view of Fig. 9 , where sensing polymer is coated on the barbules. More particularly, the sensing polymer is coated on the inner faces of the barbules, and anti-irritation medicine (medicine preventing skin from irritation) is coated on outer faces of the barbules.
  • the sensing polymer is a molecule selected from the group consisting of an antibody, an aptamer, a single-chain variable fragment (ScFv), a carbohydrate, glucose oxidase (GOx), hydroxybutyrate dehydrogenase (HBHD), and a combination thereof.
  • the transdermal microneedle array patch having barbules coated with the sensing polymer can sense the concentration data of hypodermal target molecules and determine the current physiological condition of user with the concentration data.
  • Fig. 11 refers to another further development of the first embodiment and shows a partially sectional view of Fig. 9 , where sensing polymer is coated on a test strip.
  • the embodiment shown in this figure is different with the embodiment of Fig. 10 in that the first microneedle set 22 in this embodiment is used to withdraw interstitial fluid. Therefore, the sensing polymer is coated on a test strip below the first microneedle set 22 instead of coating on the barbules.
  • the test strip is arranged between the first microneedle set 22 and the substrate 10.
  • the test strip comprises a conductive layer 92 and a plurality of test areas 94 on the conductive layer 92.
  • the test areas 94 are coated with sensing polymer and aligned with the through holes 2222 of the first microneedle set 22.
  • the test areas 94 are defined by the resin plate 96.
  • the first microneedle set 22 is fixed to the test strip by a binding layer 98.
  • a protection layer such as an epoxy-polyurethane (Epoxy-PU) film is formed on the surface of the sensing polymer and the anti-irritation medicine.
  • Epoxy-PU epoxy-polyurethane
  • a semi-permeable membrane or low oxygen permeable membrane is formed on the surface of the electrode, and then a sensing polymer is formed on the semi-permeable membrane or low oxygen permeable membrane.
  • a wireless transmission unit may further be electrically connected to the signal processing unit 41, and may transmit the sensor signal received from the signal processing unit 41 to a doctor for further review and diagnosis. If the doctor considers that immediate treatment or medication is required, he or she may then send an instruction signal to the user.
  • the wireless transmission unit 41 would receive the instruction signal and the transdermal sensor may provide a signal to remind the user to pay attention to his or her physiological status or to take medication.
  • Fig. 12 shows a partially sectional view of an assembled transdermal microneedles continuous monitoring system according to a fifth embodiment of the present invention.
  • the conductive pin 2248 is bent to electrically connect the contact 42 on the circuit board 40, thus dispensing with the conductive post.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Surgery (AREA)
  • Veterinary Medicine (AREA)
  • Pathology (AREA)
  • Public Health (AREA)
  • Hematology (AREA)
  • Optics & Photonics (AREA)
  • Manufacturing & Machinery (AREA)
  • Emergency Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Media Introduction/Drainage Providing Device (AREA)
  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)

Claims (15)

  1. Ein transdermales Mikronadelarray-Pflaster zum Messen einer Konzentration eines hypodermalen Zielmoleküls, das Folgendes beinhaltet:
    ein Substrat (10);
    eine Mikronadeleinheit (20), die mindestens einen ersten Mikronadelsatz (22), der als Arbeitselektrode verwendet wird, und einen zweiten Mikronadelsatz (24), der als Bezugselektrode verwendet wird, beinhaltet, wobei jeder der Mikronadelsätze mindestens eine Mikronadel beinhaltet;
    eine Signalverarbeitungseinheit (41), die auf dem Substrat (10) angeordnet ist und elektrisch mit dem ersten Mikronadelsatz (22) und dem zweiten Mikronadelsatz (24) verbunden ist; und
    eine Stromversorgungseinheit (43), die dem transdermalen Mikronadelarray-Pflaster Arbeitsenergie bereitstellt,
    dadurch gekennzeichnet, dass der erste Mikronadelsatz (22) eine Vielzahl von 2, 3 oder 4 Platten (222, 224, 226, 228), die aufeinander gestapelt sind, beinhaltet, wobei jede der Platten (222, 224, 226, 228) mindestens eine darauf ausgebildete Durchgangsbohrung (2222, 2242, 2262; 2282) und einen Hakenstrahl (2224, 2244, 2264, 2284), der am Rand der Durchgangsbohrung (2222, 2242, 2262, 2282) angeordnet ist, beinhaltet, wobei die Durchgangsbohrung (2222) auf einer Platte (222) von den Hakenstrahlen (2244, 2264, 2284) anderer Platten (224, 226, 228) durchdrungen wird und die Hakenstrahlen (2224, 2244, 2264) 2284) separat eingerichtet sind.
  2. Das transdermale Mikronadelarray-Pflaster gemäß Anspruch 1, wobei der erste Mikronadelsatz (22) eine erste Platte (222) und eine zweite Platte (224), die auf der ersten Platte (222) gestapelt ist, beinhaltet, wobei die erste Platte (222) mindestens eine darauf ausgebildete erste Durchgangsbohrung (2222) und einen ersten Hakenstrahl (2224) am Rand der ersten Durchgangsbohrung (2222) aufweist, wobei die zweite Platte (224) mindestens eine darauf ausgebildete zweite Durchgangsbohrung (2242) und einen zweiten Hakenstrahl (2244) am Rand der zweiten Durchgangsbohrung (2242) aufweist, wobei der zweite Hakenstrahl (2244) die erste Durchgangsbohrung (2222) durchdringt, so dass er an einer entsprechenden Stelle neben dem ersten Hakenstrahl (2224) liegt.
  3. Das transdermale Mikronadelarray-Pflaster gemäß Anspruch 1, wobei der erste Mikronadelsatz (22) eine erste Platte (222), eine zweite Platte (224) und eine dritte Platte (226), die aufeinander gestapelt sind, beinhaltet, wobei die erste Platte (222) mindestens eine darauf ausgebildete erste Durchgangsbohrung (2222) und einen ersten Hakenstrahl (2224) am Rand der ersten Durchgangsbohrung (2222) beinhaltet, wobei die zweite Platte (224) mindestens eine darauf ausgebildete zweite Durchgangsbohrung (2242) und einen zweiten Hakenstrahl (2244) am Rand der zweiten Durchgangsbohrung (2242) aufweist, wobei die dritte Platte (226) mindestens eine darauf ausgebildete dritte Durchgangsbohrung (2262) und einen dritten Hakenstrahl (2264) am Rand der dritten Durchgangsbohrung (2262) beinhaltet, wobei der zweite Hakenstrahl (2244) und der dritte Hakenstrahl (2264) die erste Durchgangsbohrung (2222) durchdringen, so dass sie neben dem ersten Hakenstrahl (2224) liegen und die Spitzen der Hakenstrahlen (2224 2244, 2264) sich in einer dreieckigen Anordnung befinden.
  4. Das transdermale Mikronadelarray-Pflaster gemäß Anspruch 1, wobei der erste Mikronadelsatz (22) eine erste Platte (222), eine zweite Platte (224), eine dritte Platte (226) und eine vierte Platte (228), die aufeinander gestapelt sind, beinhaltet, wobei die erste Platte (222) mindestens eine darauf ausgebildete erste Durchgangsbohrung (2222) und einen ersten Hakenstrahl (2224) am Rand der ersten Durchgangsbohrung (2222) aufweist, die zweite Platte (224) mindestens eine zweite darauf ausgebildete Durchgangsbohrung (2242) und einen zweiten Hakenstrahl (2244) am Rand der zweiten Durchgangsbohrung (2242) aufweist, wobei die dritte Platte (226) mindestens eine darauf ausgebildete dritte Durchgangsbohrung (2262) und einen dritten Hakenstrahl (2264) am Rand der dritten Durchgangsbohrung (2262) aufweist, wobei die vierte Platte (228) mindestens eine darauf ausgebildete vierte Durchgangsbohrung (2282) und einen vierten Hakenstrahl (2284) am Rand der vierten Durchgangsbohrung (2282) aufweist, wobei der zweite Hakenstrahl (2244), der dritte Hakenstrahl (2264) und der vierte Hakenstrahl (2284) die erste Durchgangsbohrung (2222) durchdringen, so dass sie neben dem ersten Hakenstrahl (2224) liegen und die Spitzen der Hakenstrahlen (2224, 2244, 2264, 2284) sich in einer rechteckigen Anordnung befinden.
  5. Das transdermale Mikronadelarray-Pflaster gemäß einem der Ansprüche 1-4, wobei jeder Hakenstrahl (2224) des ersten Mikronadelsatzes (22) eine Spitze (2221) und einen Sockel (2223) beinhaltet, wobei die Spitzen der Hakenstrahlen sich nicht auf der gleichen Höhe befinden, nachdem die Platten gestapelt worden sind und die Durchgangsbohrung einer Platte von den Hakenstrahlen anderer Platten durchdrungen worden ist.
  6. Das transdermale Mikronadelarray-Pflaster gemäß einem der Ansprüche 1-4, wobei jeder Hakenstrahl (2224) des ersten Mikronadelsatzes (22) eine Spitze (2221) und einen Sockel (2223) beinhaltet, wobei die Spitzen der Hakenstrahlen sich auf der gleichen Höhe befinden, nachdem die Platten gestapelt worden sind und die Durchgangsbohrung einer Platte von den Hakenstrahlen anderer Platten durchdrungen worden ist.
  7. Das transdermale Mikronadelarray-Pflaster gemäß einem der vorhergehenden Ansprüche, wobei die Mikronadeln des ersten Mikronadelsatzes (22) und des zweiten Mikronadelsatzes (24) durch Stanzen oder Ätzen gebildet werden.
  8. Das transdermale Mikronadelarray-Pflaster gemäß einem der vorhergehenden Ansprüche, wobei jeder der Hakenstrahlen (2224) auf seiner Innenfläche mit Abtastpolymer beschichtet ist.
  9. Das transdermale Mikronadelarray-Pflaster gemäß einem der vorhergehenden Ansprüche, wobei jeder der Hakenstrahlen (2224) auf seiner Außenfläche mit reizhemmendem Arzneimittel beschichtet ist.
  10. Das transdermale Mikronadelarray-Pflaster gemäß einem der vorhergehenden Ansprüche, das ferner einen Teststreifen beinhaltet, der zwischen dem ersten Mikronadelsatz (22) und dem Substrat (10) angeordnet ist, wobei der Teststreifen eine leitende Schicht (92) und eine Vielzahl von Testflächen (94) auf der leitenden Schicht (92) beinhaltet, wobei die Testflächen (94) mit Abtastpolymer beschichtet sind und mit den Durchgangsbohrungen (2222) des ersten Mikronadelsatzes (22) ausgerichtet sind.
  11. Das transdermale Mikronadelarray-Pflaster gemäß Anspruch 8 oder Anspruch 10, wobei das Abtastpolymer ein Molekül ist, das aus der Gruppe ausgewählt ist, die aus einem Antikörper, einem Aptamer, einem einkettigen variablen Fragment (ScFv), einem Kohlenhydrat und einer Kombination davon besteht.
  12. Das transdermale Mikronadelarray-Pflaster gemäß einem der vorhergehenden Ansprüche, wobei das Material der Hakenstrahlen (2224, 2244, 2264, 2284) aus der Gruppe ausgewählt ist, die aus rostfreiem Stahl, Nickel, Nickellegierung, Titan, Titanlegierung, Kohlenstoffnanoröhrchen und Silicium besteht, wobei die Oberfläche der Hakenstrahlen mit biologisch kompatiblem Metall beschichtet ist.
  13. Das transdermale Mikronadelarray-Pflaster gemäß einem der vorhergehenden Ansprüche. wobei das Material der Hakenstrahlen (2224, 2244, 2264, 2284) Harz ist, wobei die Oberfläche der Hakenstrahlen (2224, 2244, 2264, 2284) mit biologisch kompatiblem Metall beschichtet ist.
  14. Ein Verfahren zum Herstellen des transdermalen Mikronadelarray-Pflasters, das die folgenden Schritte beinhaltet:
    Bereitstellen eines Substrats und einer Mikronadeleinheit gemäß Anspruch 1; Beschichten der Oberfläche der Hakenstrahlen des ersten Mikronadelsatzes der Mikronadeleinheit mit einer biologisch kompatiblen Metallschicht;
    Bilden einer selbstorganisierenden Monoschicht auf der biologisch kompatiblen Metallschicht;
    Koppeln eines Antikörpers oder eines Aptamers mit der selbstorganisierenden Monoschicht; und
    Aufbringen eines Blockiermoleküls auf eine Position, an welcher der Antikörper oder das Aptamer nicht auf der selbstorganisierenden Monoschicht gekoppelt wird.
  15. Verfahren zum Herstellen eines transdermalen Mikronadelarray-Pflasters gemäß Anspruch 14, das ferner in die biologisch kompatible Metallschicht hineingemischte Kohlenstoffnanoröhrchen beinhaltet.
EP14171688.6A 2014-01-28 2014-06-10 Transdermales Mikronadel-Array-Pflaster und Herstellungsverfahren dafür Active EP2898821B1 (de)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
TW103103312A TWI519781B (zh) 2014-01-28 2014-01-28 經皮微針陣列貼布

Publications (2)

Publication Number Publication Date
EP2898821A1 EP2898821A1 (de) 2015-07-29
EP2898821B1 true EP2898821B1 (de) 2017-12-06

Family

ID=50897444

Family Applications (1)

Application Number Title Priority Date Filing Date
EP14171688.6A Active EP2898821B1 (de) 2014-01-28 2014-06-10 Transdermales Mikronadel-Array-Pflaster und Herstellungsverfahren dafür

Country Status (3)

Country Link
US (1) US10034636B2 (de)
EP (1) EP2898821B1 (de)
TW (1) TWI519781B (de)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11478194B2 (en) 2020-07-29 2022-10-25 Biolinq Incorporated Continuous analyte monitoring system with microneedle array
US11857344B2 (en) 2021-05-08 2024-01-02 Biolinq Incorporated Fault detection for microneedle array based continuous analyte monitoring device
US11963796B1 (en) 2021-06-16 2024-04-23 Biolinq Incorporated Heterogeneous integration of silicon-fabricated solid microneedle sensors and CMOS circuitry

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015009970A1 (en) 2013-07-18 2015-01-22 Erythron Llc Spectroscopic measurements with parallel array detector
TWI543799B (zh) * 2014-01-28 2016-08-01 微凸科技股份有限公司 乳酸量測裝置及運動訓練調整的方法
US20150338338A1 (en) 2014-02-28 2015-11-26 Erythron, Llc Method and Apparatus for Determining Markers of Health by Analysis of Blood
US20180338712A1 (en) * 2014-07-17 2018-11-29 Imperial Innovations Limited Mutli-probe microstructured arrays
TWI626965B (zh) * 2015-01-29 2018-06-21 黃榮堂 經皮微針管單元及其構成的經皮微針管投藥裝置
WO2016144073A1 (ko) * 2015-03-06 2016-09-15 삼성전자 주식회사 생체 정보 측정 장치
EP3282937A4 (de) 2015-04-14 2018-11-21 Nueon Inc. Verfahren und vorrichtung zur bestimmung von gesundheitsmarkern durch die analyse von blut
WO2017165403A1 (en) 2016-03-21 2017-09-28 Nueon Inc. Porous mesh spectrometry methods and apparatus
WO2017184895A2 (en) * 2016-04-20 2017-10-26 Aelan Cell Technologies, Inc. Compositions and methods related to κ180 dimethylated h1.0 protein
US20200008299A1 (en) * 2016-10-21 2020-01-02 Bao Tran Flexible printed electronics
WO2018085699A1 (en) 2016-11-04 2018-05-11 Nueon Inc. Combination blood lancet and analyzer
JP2020504749A (ja) * 2016-12-28 2020-02-13 ネクスモス カンパニー リミテッドＮｅｘｍｏｓ Ｃｏ．，Ｌｔｄ． アプタマーでコーティングされたマイクロニードルベースの診断用皮膚パッチの製造方法及びそのパッチ
US11412959B2 (en) * 2017-02-10 2022-08-16 Epicore Biosystems, Inc. EAB sensing devices with biofluid sample concentration
US20190038191A1 (en) * 2017-08-07 2019-02-07 Zansors Llc Glucose sensors and methods for detecting glucose in bodily fluids
EP3700569A4 (de) 2017-10-25 2021-08-25 Aelan Cell Technologies, Inc. H1.0k180me2-antikörper, verfahren zur herstellung und verwendungen davon
JP7430140B2 (ja) * 2018-06-26 2024-02-09 久光製薬株式会社 マイクロニードルデバイス及びそれを製造する方法
US11809382B2 (en) 2019-04-01 2023-11-07 Nutanix, Inc. System and method for supporting versioned objects
AU2020359292A1 (en) * 2019-10-01 2022-04-21 WearOptimo Pty Ltd Analyte measurement system
US20210196141A1 (en) * 2019-12-27 2021-07-01 RichHealth Technology Corporation Wearable sensing device
US20220008007A1 (en) * 2020-07-13 2022-01-13 Icreate Technology (Zhuhai) Co., Ltd. Microneedle array and sensor including the same
US11900164B2 (en) 2020-11-24 2024-02-13 Nutanix, Inc. Intelligent query planning for metric gateway
US11822370B2 (en) 2020-11-26 2023-11-21 Nutanix, Inc. Concurrent multiprotocol access to an object storage system
CN115245332A (zh) * 2021-04-27 2022-10-28 华为技术有限公司 电子设备、贴片及检测系统
AU2022306407A1 (en) 2021-07-07 2024-02-22 The Regents Of The University Of California Wearable, non-intrusive microneedle sensor
WO2023172522A1 (en) * 2022-03-07 2023-09-14 The Regents Of The University Of California Wearable aptamer microneedle patch for continuous minimally-invasive biomonitoring

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7344499B1 (en) 1998-06-10 2008-03-18 Georgia Tech Research Corporation Microneedle device for extraction and sensing of bodily fluids
EP1416980A2 (de) * 1999-12-30 2004-05-12 Redeon, Inc. Stapelbare mikronadel-systeme
US20060036209A1 (en) * 2003-11-13 2006-02-16 Janardhanan Subramony System and method for transdermal delivery
US7785301B2 (en) * 2006-11-28 2010-08-31 Vadim V Yuzhakov Tissue conforming microneedle array and patch for transdermal drug delivery or biological fluid collection
US8588884B2 (en) * 2010-05-28 2013-11-19 Emkinetics, Inc. Microneedle electrode
EP2750754B1 (de) * 2011-09-02 2021-03-24 The Regents of the University of California Mikronadelfelder für biosensing und wirkstofffreisetzung
TWM427950U (en) * 2011-09-23 2012-05-01 Univ Nat Taipei Technology Transdermal sensor
TWI548395B (zh) * 2014-01-28 2016-09-11 微凸科技股份有限公司 連續經皮微針監測系統
TWI543799B (zh) * 2014-01-28 2016-08-01 微凸科技股份有限公司 乳酸量測裝置及運動訓練調整的方法

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11478194B2 (en) 2020-07-29 2022-10-25 Biolinq Incorporated Continuous analyte monitoring system with microneedle array
US11872055B2 (en) 2020-07-29 2024-01-16 Biolinq Incorporated Continuous analyte monitoring system with microneedle array
US11857344B2 (en) 2021-05-08 2024-01-02 Biolinq Incorporated Fault detection for microneedle array based continuous analyte monitoring device
US11963796B1 (en) 2021-06-16 2024-04-23 Biolinq Incorporated Heterogeneous integration of silicon-fabricated solid microneedle sensors and CMOS circuitry

Also Published As

Publication number Publication date
TW201530129A (zh) 2015-08-01
US20150208985A1 (en) 2015-07-30
EP2898821A1 (de) 2015-07-29
TWI519781B (zh) 2016-02-01
US10034636B2 (en) 2018-07-31

Similar Documents

Publication Publication Date Title
EP2898821B1 (de) Transdermales Mikronadel-Array-Pflaster und Herstellungsverfahren dafür
US11830955B2 (en) Transdermal microneedle continuous monitoring system
Teymourian et al. Lab under the skin: microneedle based wearable devices
US20210076988A1 (en) Non-invasive and wearable chemical sensors and biosensors
Chen et al. Skin-like biosensor system via electrochemical channels for noninvasive blood glucose monitoring
TWI730504B (zh) 經皮微針監測系統
García-Guzmán et al. Microneedle based electrochemical (Bio) Sensing: Towards decentralized and continuous health status monitoring
US20130225956A1 (en) Transdermal Sensor
Chinnadayyala et al. review—in vivo and in vitro microneedle based enzymatic and non-enzymatic continuous glucose monitoring biosensors
Zhang et al. Microneedle-assisted technology for minimally invasive medical sensing
EP3381370B1 (de) Transdermales mikronadelfeldpflaster
EP3448258A1 (de) Multiplexte transdermale extraktions- und detektionsvorrichtungen zur nichtinvasiven überwachung von substanzen und verfahren zur verwendung
Chen et al. Silk-based electrochemical sensor for the detection of glucose in sweat
Yang et al. Masticatory system–inspired microneedle theranostic platform for intelligent and precise diabetic management
Fang et al. Semi-implantable bioelectronics
CN104970805B (zh) 经皮微针阵列贴布及其制造方法
TWI666034B (zh) 經皮微針陣列貼布
Lyu et al. Soft, disruptive and wearable electrochemical biosensors
EP3841975B1 (de) Erfassende wearable-vorrichtung
Tehrani Lab-Under-The-Skin: A Microneedle Platform for Electrochemical Wearable Sensing
Li Brief Description and Application of Microneedle Biosensors
JP2004033374A (ja) 体内情報検出ユニット
CN116849646A (zh) 一种基于碳纳米管复合微针的植入式葡萄糖电极
JPWO2020257069A5 (de)

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20141229

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

AX Request for extension of the european patent

Extension state: BA ME

17Q First examination report despatched

Effective date: 20160224

RIC1 Information provided on ipc code assigned before grant

Ipc: A61B 5/145 20060101ALN20170504BHEP

Ipc: A61B 5/15 20060101ALI20170504BHEP

Ipc: A61B 5/00 20060101AFI20170504BHEP

Ipc: A61N 1/04 20060101ALI20170504BHEP

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

RIC1 Information provided on ipc code assigned before grant

Ipc: A61B 5/00 20060101AFI20170515BHEP

Ipc: A61B 5/145 20060101ALN20170515BHEP

Ipc: A61N 1/04 20060101ALI20170515BHEP

Ipc: A61B 5/15 20060101ALI20170515BHEP

RIC1 Information provided on ipc code assigned before grant

Ipc: A61N 1/04 20060101ALI20170606BHEP

Ipc: A61B 5/15 20060101ALI20170606BHEP

Ipc: A61B 5/00 20060101AFI20170606BHEP

Ipc: A61B 5/145 20060101ALN20170606BHEP

INTG Intention to grant announced

Effective date: 20170622

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: AT

Ref legal event code: REF

Ref document number: 951606

Country of ref document: AT

Kind code of ref document: T

Effective date: 20171215

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 602014018095

Country of ref document: DE

REG Reference to a national code

Ref country code: NL

Ref legal event code: MP

Effective date: 20171206

REG Reference to a national code

Ref country code: LT

Ref legal event code: MG4D

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: ES

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

Ref country code: LT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

Ref country code: SE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

Ref country code: NO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20180306

Ref country code: FI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

REG Reference to a national code

Ref country code: AT

Ref legal event code: MK05

Ref document number: 951606

Country of ref document: AT

Kind code of ref document: T

Effective date: 20171206

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20180307

Ref country code: LV

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

Ref country code: RS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

Ref country code: HR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

Ref country code: BG

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20180306

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: NL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: EE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: AT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

Ref country code: PL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

Ref country code: SM

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

Ref country code: IT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

Ref country code: RO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 602014018095

Country of ref document: DE

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

26N No opposition filed

Effective date: 20180907

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

Ref country code: DK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

REG Reference to a national code

Ref country code: BE

Ref legal event code: MM

Effective date: 20180630

REG Reference to a national code

Ref country code: IE

Ref legal event code: MM4A

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MC

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20180610

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20180630

Ref country code: IE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20180610

Ref country code: LI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20180630

Ref country code: FR

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20180630

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20180630

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20180610

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: TR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MK

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20171206

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

Ref country code: HU

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT; INVALID AB INITIO

Effective date: 20140610

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: AL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20171206

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20180406

REG Reference to a national code

Ref country code: DE

Ref legal event code: R081

Ref document number: 602014018095

Country of ref document: DE

Owner name: RICHHEALTH TECHNOLOGY CORPORATION, ZHUBEI, TW

Free format text: FORMER OWNER: MICRO NIPPLE TECHNOLOGY CO., LTD., TAIPEI CITY, TW

Ref country code: GB

Ref legal event code: 732E

Free format text: REGISTERED BETWEEN 20210916 AND 20210922

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 20230627

Year of fee payment: 10

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20230622

Year of fee payment: 10